BACKGROUND: B cells receive activating signals from T cells through CD40, from microbial DNA through Toll-like receptor (TLR) 9, and from dendritic cells through transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI). TLR9 and CD40 ligation augment TACI-driven B-cell activation, but only the mechanism of synergy between CD40 and TACI has been explored. Synergy between CD40 and TLR9 in B-cell activation is controversial. OBJECTIVE: We sought to examine the mechanisms by which TLR9 modulates CD40- and TACI-mediated activation of B cells and to determine whether all 3 receptors synergize to activate B cells. METHODS: Naive murine B cells and human PBMCs were stimulated with combinations of anti-CD40, CpG, and a proliferation inducing ligand in the presence of IL-4. Proliferation was measured by means of tritiated thymidine incorporation. Immunoglobulin production was measured by means of ELISA. Class-switch recombination (CSR) was examined by measuring mRNA for germline transcripts, activation-induced cytidine deaminase (AICDA), and mature immunoglobulin transcripts. Plasma cell differentiation was examined by using syndecan-1/CD138 staining and mRNA expression of B lymphocyte-induced maturation protein 1 (Blimp-1). RESULTS: TLR9 synergized with CD40 and TACI in driving CSR and inducing IgG(1) and IgE secretion by naive murine B cells and synergized with TACI in driving B-cell proliferation and plasma cell differentiation. All 3 receptors synergized together in driving murine B-cell proliferation, CSR, plasma cell differentiation, and IgG(1) and IgE secretion. TLR9 synergized with CD40 and TACI in driving IgG secretion in IL-4-stimulated human B cells. CONCLUSION: Signals from TLR9, TACI, and CD40 are integrated to promote B-cell activation and differentiation.
BACKGROUND: B cells receive activating signals from T cells through CD40, from microbial DNA through Toll-like receptor (TLR) 9, and from dendritic cells through transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI). TLR9 and CD40 ligation augment TACI-driven B-cell activation, but only the mechanism of synergy between CD40 and TACI has been explored. Synergy between CD40 and TLR9 in B-cell activation is controversial. OBJECTIVE: We sought to examine the mechanisms by which TLR9 modulates CD40- and TACI-mediated activation of B cells and to determine whether all 3 receptors synergize to activate B cells. METHODS: Naive murine B cells and human PBMCs were stimulated with combinations of anti-CD40, CpG, and a proliferation inducing ligand in the presence of IL-4. Proliferation was measured by means of tritiated thymidine incorporation. Immunoglobulin production was measured by means of ELISA. Class-switch recombination (CSR) was examined by measuring mRNA for germline transcripts, activation-induced cytidine deaminase (AICDA), and mature immunoglobulin transcripts. Plasma cell differentiation was examined by using syndecan-1/CD138 staining and mRNA expression of B lymphocyte-induced maturation protein 1 (Blimp-1). RESULTS:TLR9 synergized with CD40 and TACI in driving CSR and inducing IgG(1) and IgE secretion by naive murine B cells and synergized with TACI in driving B-cell proliferation and plasma cell differentiation. All 3 receptors synergized together in driving murine B-cell proliferation, CSR, plasma cell differentiation, and IgG(1) and IgE secretion. TLR9 synergized with CD40 and TACI in driving IgG secretion in IL-4-stimulated human B cells. CONCLUSION: Signals from TLR9, TACI, and CD40 are integrated to promote B-cell activation and differentiation.
Authors: M Yan; H Wang; B Chan; M Roose-Girma; S Erickson; T Baker; D Tumas; I S Grewal; V M Dixit Journal: Nat Immunol Date: 2001-07 Impact factor: 25.606
Authors: S Ferrari; S Giliani; A Insalaco; A Al-Ghonaium; A R Soresina; M Loubser; M A Avanzini; M Marconi; R Badolato; A G Ugazio; Y Levy; N Catalan; A Durandy; A Tbakhi; L D Notarangelo; A Plebani Journal: Proc Natl Acad Sci U S A Date: 2001-10-23 Impact factor: 11.205
Authors: Scott R Brodeur; Federica Angelini; Leonard B Bacharier; Anna M Blom; Emiko Mizoguchi; Hiroshi Fujiwara; Alessandro Plebani; Luigi D Notarangelo; Bjorn Dahlback; Erdyni Tsitsikov; Raif S Geha Journal: Immunity Date: 2003-06 Impact factor: 31.745
Authors: Matthew A Pettengill; Simon D van Haren; Ning Li; David J Dowling; Ilana Bergelson; Jop Jans; Gerben Ferwerda; Ofer Levy Journal: Innate Immun Date: 2016-06-01 Impact factor: 2.680
Authors: Maria B Almejun; Montserrat Cols; Marta Zelazko; Matias Oleastro; Andrea Cerutti; Pablo Oppezzo; Charlotte Cunningham-Rundles; Silvia Danielian Journal: Eur J Immunol Date: 2013-01-18 Impact factor: 5.532